For the past several years, we have been studying regulation of protein synthesis in rat liver, concentrating primarily on molecular events controlling albumin synthesis and albumin mRNA-ribosome-membrane interaction. We have purified albumin mRNA and developed molecular hybridization technology (alb (3H) -cDNA probe) in conjunction with cell-free protein synthesis to examine subcellular levels, distribution and function of albumin mRNA in both normal liver and certain pathophysiologic states (protein-calorie deprivation and chronic renal failure). We are currently cloning albumin cDNA in E. coli under appropriate precautions according to NIH guidelines for Recombinant DNA research and have obtained a number of clones which can be used as purified albumin DNA probes. With molecular probes in large quantity, we will continue our studies of subcellular distribution and function of albumin mRNA in various pathophysiologic states (acute vs chronic protein calorie malnutrition, acute versus chronic ETOH administration, CCl4 induced cirrhosis, liver regeneration and hepatocellular carcinomas). We will also begin studies on the nuclear synthesis, processing and metabolism of albumin mRNA beginning with tissue culture cell lines from normal liver and hepatomas. We will also use our albumin cDNA probe to initiate studies of the albumin structural gene in normal liver and certain pathologic models, as well as in normal development and hepatoma cell lines. Studies of albumin mRNA synthesis and metabolism are critical in assessing albumin gene function (at both the transcriptional and post-transcriptional level) in normal liver and pathophysiologic states. In this way, we hope to gain a better understanding of basic molecular events in albumin synthesis, as well as gain new insight into abnormalities in protein synthesis in various forms of liver disease.